tbuckley/cabot-search huggingface dataset:
COVID-19-related changes in outpatient CPAP setup pathways for OSA are linked with decreased 30-day CPAP usage
Authors: Chris D Turnbull, Martin Allen, Jennifer Appleby, Richard Brown, Nathalie Bryan, Ann Cooper, Brendan G Cooper, Cathie Gillooly, James Davidson, Hannah Farley, Ana Gaspar, Gillian Gibbons, Beverley Gray, Graham Hill, Adrian Kendrick, Blake Marsh, Alison McMillan, Joseph Page, Justin Charles Thane Pepperell, Tim Quinnell, Chris Rogers, Jane Sexton, Naomi Sheperd, Joerg Steier, James Stockley, John Stradling, Asia Woroszyl, Sophie West, Susan Wright, Annabel Nickol
Journal: Thorax (2022)

The COVID-19 pandemic changed continuous positive airway pressure (CPAP) setup pathways. We evaluated patients commenced on CPAP in 2019 (prepandemic) and 2020 (post-first UK wave). Face-to-face (F2F) setup numbers, with CPAP turned on, decreased from 613 patients (98.9%) in 2019, to 6 (1.1%) in 2020. In 2020, setups were F2F without CPAP turned on (403 (71.1%)), or remote (158 (27.9%)). Prepandemic median CPAP usage at first follow-up was 5.4 (2.7–6.9) hours/night and fell by 0.9 hours/night (95% CI 0.5 to 1.2, p&lt;0.0001) in 2020. We found clinically relevant reductions in CPAP usage with pathway changes post-COVID-19.
Is Regional Nodal Radiotherapy Necessary for Patients With cN1 and ypN0 Breast Cancer After Neoadjuvant Chemotherapy?
Authors: Yanhong Wang, Yi Ouyang, Qunrong Cai
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Thrombolytic tPA-Induced Hemorrhagic Transformation of Ischemic Stroke is Mediated by PKCβ phosphorylation of Occludin
Authors: Andreia Goncalves, Enming J Su, Arivalagan Muthusamy, Manuel Zeitelhofer, Daniel Torrente, Ingrid Nilsson, Jil Protzmann, Linda Fredriksson, Ulf Eriksson, David A Antonetti, Daniel A Lawrence
Journal: Blood (2022)

The current standard of care for moderate to severe ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA). Treatment with tPA can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intracerebral hemorrhage (ICH). The risk of hemorrhage significantly limits the use of thrombolytic therapy and identifying pathways induced by tPA that increase this risk could provide new therapeutic options to extend thrombolytic therapy to a wider patient population. Here, we investigate the role of protein kinase (PK)Cβ phosphorylation of the tight junction protein occludin during ischemic stroke and its role in cerebrovascular permeability. We demonstrate that activation of this pathway by tPA is associated with an increased risk of ICH. Middle cerebral artery occlusion (MCAO) increased occludin serine 490 (S490) phosphorylation in the ischemic penumbra in a tPA-dependent manner, as tPA-/- mice were significantly protected from MCAO-induced occludin phosphorylation. Intra-ventricular injection of tPA in the absence of ischemia was sufficient to induce occludin phosphorylation and vascular permeability in a PKCb-dependent manner. Blocking occludin phosphorylation either by targeted expression of a non-phosphorylatable form of occludin (S490A) or by pharmacologic inhibition of PKCβ, reduced MCAO-induced permeability and improved functional outcome. Further, inhibiting PKCβ after MCAO prevented ICH associated with delayed thrombolysis. These results reveal that PKCβ phosphorylation of occludin is a downstream mediator of tPA-induced cerebrovascular permeability and suggest that PKCb inhibitors could improve stroke outcome and prevent ICH associated with delayed thrombolysis, potentially extending the window for thrombolytic therapy in stroke.
Preeclampsia
Authors: Laura A. Magee, Kypros H. Nicolaides, Peter von Dadelszen
Journal: New England Journal of Medicine (2022)

Preeclampsia complicates 2 to 4% of all pregnancies and accounts for about 46,000 maternal deaths and 500,000 fetal or newborn deaths each year. Antihypertensive agents and magnesium sulfate can help control the systemic manifestations of preeclampsia, which is usually resolved by delivery of the placenta.
Reduction of antibacterial use in patients with very low birth weight on German NICUs after implementation of a mandatory surveillance system. A longitudinal study with national data from 2013 to 2019
Authors: Tobias Siegfried Kramer, Florian Salm, Frank Schwab, Christine Geffers, Michael Behnke, Petra Gastmeier, Brar Piening
Journal: Journal of Infection (2022)
Abstract A038: Does mutation rate of cancer cells change as the stage of the disease advances?
Authors: Fargam Neinavaie, Andrew Kramer
Journal: Cancer Research (2022)

Abstract Tumorigenesis begins with cells that have normal mutation rates. As the cells become immortal and accumulate different numbers of mutations along the way, current literature splits in two describing if and how mutation rates increase as the cancer progresses. Some argue that as the mutation rates are small (mutation rate in healthy cells is per nucleotide site per cell division) and malignant cells are loaded with thousands of different types of mutations, they must have acquired a mutator phenotype early in their development. Others argue that immortality of malignant cells, and their rate of proliferation is responsible for their genetic instability and number of mutations observed in their genome. We conduct a review of the literature with the key words “mutation rate” and “cancer” in their title. We review 123 papers and found that description of mutation rates varied in the published work. This leads to estimates of mutation rates in cancer from per nucleotide site per cell division. Some of this variation in mutational rates arises across different organs of the body, for instance liver cells have a higher mutation rate than heart and brain. Cancer treatments such as chemotherapy influence mutation rate, and mutation rate of drug and multidrug resistance cancer cell is higher than newly diagnosed cancer cells. Further, mutation rate is defined differently in different literature, some papers measure the mutation rate in a population or a gene, some calculate it per base pair, genome, or mitosis. Here we provide a comprehensive picture of published mutation rates across different cancer types in order to inform cancer models and treatment plans for individual patients. We propose a unified framework for discussing and reporting mutation rate of cancer cells and formulations on how to switch between definitions. Citation Format: Fargam Neinavaie, Andrew Kramer. Does mutation rate of cancer cells change as the stage of the disease advances? [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A038.
METTL3-mediated m6A RNA methylation regulates dorsal lingual epithelium homeostasis
Authors: Qiuchan Xiong, Caojie Liu, Xin Zheng, Xinyi Zhou, Kexin Lei, Xiaohan Zhang, Qian Wang, Weimin Lin, Ruizhan Tong, Ruoshi Xu, Quan Yuan
Journal: International Journal of Oral Science (2022)

Abstract The dorsal lingual epithelium, which is composed of taste buds and keratinocytes differentiated from K14 + basal cells, discriminates taste compounds and maintains the epithelial barrier. N6-methyladenosine (m 6 A) is the most abundant mRNA modification in eukaryotic cells. How METTL3-mediated m 6 A modification regulates K14 + basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear. Here we show knockout of Mettl3 in K14 + cells reduced the taste buds and enhanced keratinocytes. Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds. Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization, but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery. Mechanically, we revealed that the most frequent m 6 A modifications were enriched in Hippo and Wnt signaling, and specific peaks were observed near the stop codons of Lats1 and FZD7 . Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.
Taking social psychology out of context
Authors: Michael Brownstein, Daniel Kelly, Alex Madva
Journal: Behavioral and Brain Sciences (2022)

Abstract We endorse Cesario's call for more research into the complexities of “real-world” decisions and the comparative power of different causes of group disparities. Unfortunately, these reasonable suggestions are overshadowed by a barrage of non sequiturs, misdirected criticisms of methodology, and unsubstantiated claims about the assumptions and inferences of social psychologists.
National Cohort Study of Health Care Resource Use After Pediatric Tracheostomy
Authors: Jason Powell, Kim Keltie, Andrew Sims, Hayley Richardson, Malcolm Brodlie, Steven Powell
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model
Authors: Reinier G S Meester, Hilliene J van de Schootbrugge-Vandermeer, Emilie C H Breekveldt, Lucie de Jonge, Esther Toes-Zoutendijk, Arthur Kooyker, Daan Nieboer, Christian R Ramakers, Manon C W Spaander, Anneke J van Vuuren, Ernst J Kuipers, Folkert J van Kemenade, Iris D Nagtegaal, Evelien Dekker, Monique E van Leerdam, Iris Lansdorp-Vogelaar
Journal: Gut (2022)

To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC).Prognostic model.Dutch biennial FIT-based screening programme during 2014-2018.265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2.Colonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces).We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation.Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91).Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.
Erythroid lineage Jak2V617F expression promotes atherosclerosis through erythrophagocytosis and macrophage ferroptosis
Authors: Wenli Liu, Nataliya Östberg, Mustafa Yalcinkaya, Huijuan Dou, Kaori Endo-Umeda, Yang Tang, Xintong Hou, Tong Xiao, Trevor P. Fidler, Sandra Abramowicz, Yong-Guang Yang, Oliver Soehnlein, Alan R. Tall, Nan Wang
Journal: Journal of Clinical Investigation (2022)

Elevated hematocrit is associated with cardiovascular risk; however, the causality and mechanisms are unclear. The JAK2V617F (Jak2VF) mutation increases cardiovascular risk in myeloproliferative disorders and in clonal hematopoiesis. Jak2VF mice with elevated WBCs, platelets, and RBCs display accelerated atherosclerosis and macrophage erythrophagocytosis. To investigate whether selective erythroid Jak2VF expression promotes atherosclerosis, we developed hyperlipidemic erythropoietin receptor Cre mice that express Jak2VF in the erythroid lineage (VFEpoR mice). VFEpoR mice without elevated blood cell counts showed increased atherosclerotic plaque necrosis, erythrophagocytosis, and ferroptosis. Selective induction of erythrocytosis with low-dose erythropoietin further exacerbated atherosclerosis with prominent ferroptosis, lipid peroxidation, and endothelial damage. VFEpoR RBCs had reduced antioxidant defenses and increased lipid hydroperoxides. Phagocytosis of human or murine WT or JAK2VF RBCs by WT macrophages induced ferroptosis, which was prevented by the ferroptosis inhibitor liproxstatin-1. Liproxstatin-1 reversed increased atherosclerosis, lipid peroxidation, ferroptosis, and endothelial damage in VFEpoR mice and in Jak2VF chimeric mice simulating clonal hematopoiesis, but had no impact in controls. Erythroid lineage Jak2VF expression led to qualitative and quantitative defects in RBCs that exacerbated atherosclerosis. Phagocytosis of RBCs by plaque macrophages promoted ferroptosis, suggesting a therapeutic target for reducing RBC-mediated cardiovascular risk.
Powering Through Daily Activities in Older Age—Will Power Training Replace Strength Training in Later Life?
Authors: On-Yee Lo, Melike Kahya, Brad Manor
Journal: JAMA Network Open (2022)

Anoop T. Balachandran, PhD; James Steele, PhD; Daniel Angielczyk, MS; Mark Belio, BS; Brad J. Schoenfeld, PhD; Norberto Quiles, PhD; Nicole Askin, MLIS; Ahmed M. Abou-Setta, MD, PhD
Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma
Authors: Gino Kim In, Aparna Nallagangula, Jacob Seung Choi, Lisa Tachiki, Matthew J Blackburn, Stephen Capone, Kathryn B Bollin, Daniel Y. Reuben, Keisuke Shirai, Sandy Zhang-Nunes, Omar Ragab, Alicia Terando, Jenny C. Hu, Han Lee, Shailender Bhatia, Sunandana Chandra, Jose Lutzky, Geoffrey Thomas Gibney
Journal: Journal for ImmunoTherapy of Cancer (2022)

Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.We conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.A total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.The clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.
Progress Toward Polio Eradication — Worldwide, January 2020–April 2022
Authors: Audrey Rachlin, Jaymin C. Patel, Cara C. Burns, Jaume Jorba, Graham Tallis, Aidan O’Leary, Steven G.F. Wassilak, John F. Vertefeuille
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In 1988, the World Health Assembly established the Global Polio Eradication Initiative (GPEI). Since then, wild poliovirus (WPV) cases have decreased approximately 99.99%, and WPV types 2 and 3 have been declared eradicated. Only Afghanistan and Pakistan have never interrupted WPV type 1 (WPV1) transmission. This report describes global progress toward polio eradication during January 1, 2020-April 30, 2022, and updates previous reports (1,2). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* Five WPV1 cases were reported from Afghanistan and Pakistan in 2021, compared with 140 in 2020. In 2022 (as of May 5), three WPV1 cases had been reported: one from Afghanistan and two from Pakistan. WPV1 genetically linked to virus circulating in Pakistan was identified in Malawi in a child with paralysis onset in November 2021. Circulating vaccine-derived polioviruses (cVDPVs), with neurovirulence and transmissibility similar to that of WPV, emerge in populations with low immunity following prolonged circulation of Sabin strain oral poliovirus vaccine (OPV) (3). During January 2020-April 30, 2022, a total of 1,856 paralytic cVDPV cases were reported globally: 1,113 in 2020 and 688 in 2021, including cases in Afghanistan and Pakistan. In 2022 (as of May 5), 55 cVDPV cases had been reported. Intensified programmatic actions leading to more effective outbreak responses are needed to stop cVDPV transmission. The 2022-2026 GPEI Strategic Plan objective of ending WPV1 transmission by the end of 2023 is attainable (4). However, the risk for children being paralyzed by polio remains until all polioviruses, including WPV and cVDPV, are eradicated.
Pollution and health: a progress update
Authors: Richard Fuller, Philip J Landrigan, Kalpana Balakrishnan, Glynda Bathan, Stephan Bose-O'Reilly, Michael Brauer, Jack Caravanos, Tom Chiles, Aaron Cohen, Lilian Corra, Maureen Cropper, Greg Ferraro, Jill Hanna, David Hanrahan, Howard Hu, David Hunter, Gloria Janata, Rachael Kupka, Bruce Lanphear, Maureen Lichtveld, Keith Martin, Adetoun Mustapha, Ernesto Sanchez-Triana, Karti Sandilya, Laura Schaefli, Joseph Shaw, Jessica Seddon, William Suk, Martha María Téllez-Rojo, Chonghuai Yan
Journal: The Lancet Planetary Health (2022)

The Lancet Commission on pollution and health reported that pollution was responsible for 9 million premature deaths in 2015, making it the world's largest environmental risk factor for disease and premature death. We have now updated this estimate using data from the Global Burden of Diseases, Injuriaes, and Risk Factors Study 2019. We find that pollution remains responsible for approximately 9 million deaths per year, corresponding to one in six deaths worldwide. Reductions have occurred in the number of deaths attributable to the types of pollution associated with extreme poverty. However, these reductions in deaths from household air pollution and water pollution are offset by increased deaths attributable to ambient air pollution and toxic chemical pollution (ie, lead). Deaths from these modern pollution risk factors, which are the unintended consequence of industrialisation and urbanisation, have risen by 7% since 2015 and by over 66% since 2000. Despite ongoing efforts by UN agencies, committed groups, committed individuals, and some national governments (mostly in high-income countries), little real progress against pollution can be identified overall, particularly in the low-income and middle-income countries, where pollution is most severe. Urgent attention is needed to control pollution and prevent pollution-related disease, with an emphasis on air pollution and lead poisoning, and a stronger focus on hazardous chemical pollution. Pollution, climate change, and biodiversity loss are closely linked. Successful control of these conjoined threats requires a globally supported, formal science-policy interface to inform intervention, influence research, and guide funding. Pollution has typically been viewed as a local issue to be addressed through subnational and national regulation or, occasionally, using regional policy in higher-income countries. Now, however, it is increasingly clear that pollution is a planetary threat, and that its drivers, its dispersion, and its effects on health transcend local boundaries and demand a global response. Global action on all major modern pollutants is needed. Global efforts can synergise with other global environmental policy programmes, especially as a large-scale, rapid transition away from all fossil fuels to clean, renewable energy is an effective strategy for preventing pollution while also slowing down climate change, and thus achieves a double benefit for planetary health.